ABSTRACT IMPACT: Genomic variation likely plays a role in differences in rates of adverse reactions and efficacy for African populations, and this research will add to the understudied field of pharmacogenomics in African populations. OBJECTIVES/GOALS: We aim to characterize the frequency of variants in clinically relevant genes in East and West African populations to assess the prevalence of potential drug-gene interactions. METHODS/STUDY POPULATION: Our pilot study will consist of 100 Somali patients enrolled at Mayo Clinic Rochester and 100 Ghanaian patients recruited at Teaching Hospitals in Ghana. Germline DNA will be extracted from pre-existing blood samples. Sequencing will be performed using Admera Health’s PGxOne Plus test, interrogating a panel of 62 genes. Variants will be reported along with the predicted response for a list of drugs. Differences between frequencies of variants in East and West African populations will be analyzed. We will look for correlations with reported adverse reaction rates. We will then compare our findings with allele frequency data from publicly available data bases. Additionally, we will analyze the flanking regions of the panel for novel variants, using machine learning to predict gene-drug interactions. RESULTS/ANTICIPATED RESULTS: African populations are known to have more genetic diversity than any other population. Additionally, only African-Americans, African-Caribbeans from Barbados, Esan and Yoruba Nigerians, Gambians, Kenyans, and Sierra Leoneans are accounted for within the publicly available data bases most often used for variant studies. Thus, it is anticipated that we will find differences in the variant allele frequencies of our populations compared to European allele frequencies, and differences in frequencies between the East and West African populations. In the 200 base pair flanking regions that are sequenced in the assay along with the known variant regions, we may find novel previously unreported variants. DISCUSSION/SIGNIFICANCE OF FINDINGS: The lack of knowledge of pharmacogenomic variation in African populations contributes to ethnic disparities in patient outcomes. This study addresses this gap by adding to our comprehension of variants in clinically relevant genes, giving insight into underlying mechanisms of ethnicity-based drug responses.

We investigated whether neurobehavioral markers of risk for emotion dysregulation were evident among newborns, as well as whether the identified markers were associated with prenatal exposure to maternal emotion dysregulation. Pregnant women (N = 162) reported on their emotion dysregulation prior to a laboratory assessment. The women were then invited to the laboratory to assess baseline respiratory sinus arrhythmia (RSA) and RSA in response to an infant cry. Newborns were assessed after birth via the NICU Network Neurobehavioral Scale. We identified two newborn neurobehavioral factors—arousal and attention—via exploratory factor analysis. Low arousal was characterized by less irritability, excitability, and motor agitation, while low attention was related to a lower threshold for auditory and visual stimulation, less sustained attention, and poorer visual tracking abilities. Pregnant women who reported higher levels of emotion dysregulation had newborns with low arousal levels and less attention. Larger decreases in maternal RSA in response to cry were also related to lower newborn arousal. We provide the first evidence that a woman's emotion dysregulation while pregnant is associated with risks for dysregulation in her newborn. Implications for intergenerational transmission of emotion dysregulation are discussed.

Two wild oat (Avena fatua L.) biotypes and two barley (Hordeum vulgare L.) varieties known to have intraspecific differential response to foliarly-applied 4-chloro-2-butynyl m-chlorocarbanilate (barban) were studied. When barban was applied to the roots, the intraspecific differential response (measured by shoot retardation) was maintained in both species but to a much lesser extent than previously observed with foliar application. Wild oat maintained a greater differential response than barley. Therefore, the factors causing the differential response to foliarly-applied barban may reside primarily in the leaves of both species but to some extent elsewhere (perhaps at the plant apex) in the wild oat biotypes and to a lesser extent elsewhere in the barley varieties. Differential response to foliar applications was not caused by differential uptake, but may be caused primarily by the susceptible biotype or variety's reduced ability to degrade barban beyond 3-chloroaniline. This might cause the greater build-up of compound X (a water-soluble 3-chloroaniline-containing metabolite of barban) observed in the susceptible biotype or variety. Compound X appeared to be nonphytotoxic. The build-up of compound X in turn may reduce the rate of metabolism of barban resulting in the greater amount of free barban found in the treated leaf of the susceptible biotype or variety 12 to 24 hr after treatment. This greater amount of free barban in the leaf of the susceptible biotype or variety may be responsible for the differential response to foliar applications of barban. Evidence for this partial explanation of the differential response was better for barley than for wild oat.

We evaluated 214 lines of wild oat (Avena fatua L.) for response to S-2,3-dichloroallyl N,N-diisopropylthiolcarbamate (diallate), S-2,3,3-trichloroaHyl N,N-diisopropylthiolcarbamate (triallate), and 4-chloro-2-butynl m-chlorocarbanilate (barban). We found large differences among the lines in response to these herbicides and some lines that might not be controlled by recommended rates of these herbicides. Frequency distributions of response to herbicides suggest that reaction to these three herbicides is quantitatively inherited. We were unable to establish a relationship between morphological characteristics and plant response to these herbicides.

Further information is presented relating to a sledge discovered on Byers Peninsula, Livingston Island, South Shetland Islands in 2007.

Before paediatric cardiology emerged as a specialty in the mid 20th century, a body of literature had developed over centuries devoted to description of congenitally malformed hearts. In this review, we have selected highlights from such texts written during the period of 100 years from 1814 to 1914, demonstrating their potential relevance to controversies occurring during the twentieth century in the categorisation of such hearts. We begin in 1814, with the first wide-ranging book devoted to congenital cardiac malformations. We end with a publication from 1914, because it included an illustration of the first electrocardiogram in a text devoted to paediatric disease. As we will show, these works from the 19th and early 20th centuries reflect topics still relevant today, namely the aetiology of cardiac malformations, clinicopathologic correlations, attempts at classification, and lack of effective treatments. Attention to their content could have served to ameliorate controversies, some of them ongoing.

Very long-chain n-3 PUFA from fish are suggested to play a role in the development of the brain. Fish oil feeding results in higher proportions of n-3 PUFA in the brains of newborn piglets. However, the effect of fish oil on the fatty acid composition of specific cerebral brain lobes in juvenile pigs is largely uninvestigated. This study examined the effect of a fish oil diet on the fatty acid composition of the frontal, parietal, temporal and occipital brain lobes in juvenile pigs (7 weeks old). Pigs were randomly allocated to a semipurified pig diet containing either 4 % (w/w) fish oil (n 19) or 4 % (w/w) high-oleic acid sunflower oil (HOSF diet, n 18) for a period of 8 weeks. The fish oil diet resulted in significantly higher proportions (%) of DHA in the frontal (10·6 (sd1·2)), parietal (10·2 (sd1·5)) and occipital brain lobes (9·9 (sd 1·3)), but not in the temporal lobe (7·7 (sd1·6)), compared with pigs fed the HOSF diet (frontal lobe, 7·5 (sd1·0); parietal lobe, 8·1 (sd 1·3); occipital lobe, 7·3 (sd1·2), temporal lobe, 6·6 (sd1·2). Moreover, the proportion of DHA was significantly lower in the temporal lobe compared with the frontal, parietal and occipital brain lobes in pigs fed a fish oil diet. In conclusion, the brains of juvenile pigs appear to be responsive to dietary fish oil, although the temporal brain lobe is less responsive compared with the other three brain lobes. The functional consequences of these differences are a challenging focus for future investigation.

Dynamic friction, wear volumes and wear morphology have been studied for sliding wear in polysilicon in ambient air at μN normal loads using on-chip micron-scale test specimens. With increasing number of wear cycles, the friction coefficients show two distinct types of behavior: (i) an increase by a factor of two and a half to a steady-state regime after peaking at three times the initial value of about 0.10 ± 0.04, with no failure after millions of cycles; (ii) an increase by a factor larger than three followed by failure after ∼105 cycles. Additionally, the average nano-scale wear coefficient sharply increased in the first ∼105 cycles up to about 10−4 and then decayed by an order of magnitude over the course of several million cycles. For both modes of behavior, abrasive wear is the governing mechanism, the difference being attributed to variations in the local surface morphology (and wear debris) between the sliding surfaces. The oxidation of worn polysilicon surfaces only affects the friction coefficient after periods of inactivity (>30 min).

Fetal bradycardia may herald fetal demise. This article highlights arrhythmic fetal bradycardia rather than bradycardia caused by perinatal distress. We briefly examine the embryonic conduction system's development and physiology and we review the classification, aetiology, evaluation, and approach to fetal bradycardia. Our aim is to provide the clinician with practical information about fetal bradycardia that enlightens causative conditions and aids management.

Extended abstract of a paper presented at Microscopy and Microanalysis 2004 in Savannah, Georgia, USA, August 1–5, 2004.